- OXLUMO Now Indicated for the Treatment of Primary Hyperoxaluria Type 1 (PH1) to Lower Urinary and Plasma Oxalate Levels in Pediatric and Adult Patients -

- Approval is Based on Positive Efficacy and Safety Results of the ILLUMINATE-C Phase 3 Study of OXLUMO in PH1 Patients with Severe Renal Impairment, Including Those on Hemodialysis -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the U.S. Food and Drug Administration (FDA) approved a label expansion for OXLUMO® (lumasiran), an RNAi therapeutic administered via subcutaneous injection, now indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate (UOx) and plasma oxalate (POx) levels in pediatric and adult patients. The approval is based on positive efficacy and safety results of the ILLUMINATE-C Phase 3 study of OXLUMO in patients with severe renal impairment, including those on hemodialysis.

PH1 is an ultra-rare genetic disease characterized by oxalate overproduction in the liver. The excess production of oxalate results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis, which can progress to kidney failure. PH1 can also lead to oxalate deposition in multiple organs beyond the kidney, a condition known as systemic oxalosis.

The FDA approval is based on positive six-month results from the ILLUMINATE-C Phase 3 study, in which OXLUMO treatment resulted in substantial reductions in POx and demonstrated an encouraging safety and tolerability profile in patients with compromised renal function, including those with kidney failure and undergoing treatment by hemodialysis. Elevated POx is directly related to the pathophysiology of oxalosis and results in systemic deposition of oxalate in extra-renal tissues, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers and other serious manifestations.1

The supplemental New Drug Application also included results from the open-label extensions of the ILLUMINATE-A and ILLUMINATE-B Phase 3 studies of pediatric and adult patients with PH1. The label has correspondingly been updated to highlight the maintenance of sustained reductions in UOx through Month 24 and Month 12, respectively.

“Today’s label expansion exemplifies Alnylam’s commitment to advancing research and innovation in support of the PH1 community. We also believe this expansion will strengthen prescribers’ confidence in OXLUMO for patients,” said Jorge Capapey, Vice President, Global Rare Disease Lead at Alnylam Pharmaceuticals. “Through the findings of the ILLUMINATE clinical development program, I am thrilled to see the potential benefit of OXLUMO, which remains the first and only FDA-approved PH1 treatment option, now be available for a broad range of people living with the ultra-rare disease, including those advanced PH1 patients undergoing hemodialysis. We extend our sincere gratitude to the patients, families and investigators involved in the research supporting this approval, without whom it would not be possible to bring this therapy to those living with PH1.”

The label expansion for OXLUMO is based on positive six-month results from ILLUMINATE-C, where treatment with lumasiran resulted in a substantial reduction in POx from baseline to Month Six in both dialysis-independent and -dependent patients. Patients in both cohorts had a reduction in POx as early as Month One. In Cohort A (N=6, dialysis-independent), treatment with OXLUMO led to a 33% least squares (LS) mean reduction in POx from baseline to Month Six (LS Mean; 95% CI: -82%, 15%), and in Cohort B (N=15, hemodialysis-dependent), treatment with OXLUMO led to a 42% LS mean reduction in POx from baseline to Month Six (LS Mean; 95% CI: -51%, 34%). OXLUMO demonstrated an encouraging safety and tolerability profile with no deaths or drug-related serious adverse events (SAEs) among enrolled patients. There were two treatment discontinuations due to adverse events (AEs) in the extension period of the study, neither of which was drug related. The most common AE related to lumasiran was injection-site reaction (ISR) reported in five of 21 patients (24%) which were all mild and transient.

“The significance of the label expansion of OXLUMO cannot be overstated, as this milestone provides crucial reassurance among a patient population with the highest unmet need, as well as their caregivers and loved ones, that OXLUMO is available in the US for patients living with PH1, including those with advanced disease,” said Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation. “We are grateful to Alnylam for their continued commitment to the PH1 community and for ensuring that all patients — no matter how severe their disease — have the same opportunity to potentially benefit from OXLUMO treatment.”

In November of 2020, OXLUMO was approved by the FDA for the treatment of PH1 to lower UOx levels in pediatric and adult patients. It was also approved by the European Medicines Agency (EMA) for the treatment of PH1 in all age groups. The Committee for Medicinal Products for Human Use (CHMP) of the EMA delivered a positive opinion recommending variation to the marketing authorization of OXLUMO based on ILLUMINATE-C data from patients with advanced PH1 in September 2022. Lumasiran is also being evaluated in a global Phase 2 study as an investigational treatment in patients with recurrent kidney stone disease and elevated UOx levels.

Visit OXLUMO.com for more information, including full Prescribing Information.

OXLUMO® (lumasiran) INDICATION AND IMPORTANT SAFETY INFORMATION

Indication

OXLUMO® (lumasiran) is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in children and adults.

Important Safety Information

Adverse Reactions

The most common (≥20%) adverse reaction reported in patients treated with OXLUMO was injection site reaction. Injection site reactions included erythema, swelling, pain, hematoma, pruritus, and discoloration.

Pregnancy and Lactation

No data are available on the use of OXLUMO in pregnant women. No data are available on the presence of OXLUMO in human milk or its effects on breastfed infants or milk production. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for OXLUMO and any potential adverse effects on the breastfed child from OXLUMO or the underlying maternal condition.

For additional information about OXLUMO, please see the accompanying full U.S. Prescribing Information.

About OXLUMO (lumasiran)

OXLUMO® (lumasiran) is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1 and depleting the GO enzyme, OXLUMO inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. OXLUMO has received regulatory approvals from the U.S. Food and Drug Administration (FDA) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients and from the European Medicines Agency (EMA) for the treatment of PH1 in all age groups.

In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A. In the ILLUMINATE-C study, OXLUMO resulted in substantial reductions in plasma oxalate in patients with advanced PH1. Across all three studies, injection site reactions (ISRs) were the most common drug-related adverse reaction.

OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly beginning one month after the last loading dose at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly.

OXLUMO should be administered by a healthcare professional. For more information about OXLUMO, visit OXLUMO.com.

About the ILLUMINATE-C Phase 3 Study

ILLUMINATE-C (NCT04152200) is a single arm, open-label, multinational Phase 3 study with a 6-month primary analysis period and an extended 54-month dosing period to evaluate the safety and efficacy of lumasiran in PH1 patients of all ages with severe renal impairment (eGFR ≤ 45 mL/min/1.73m2 or elevated serum creatinine for patients